ABSTRACT Total joint arthroplasty (TJA) is the fastest growing elective surgery in the nation. Over 7 million Americans are currently living artificial hip or knee joints and this is expected to reach epidemic proportions as a result of growing demand for improved mobility and quality of life. Although TJA is a relatively safe procedure, there is growing concern about the long-term systemic effects of chronic exposure to TJA implants. Indeed, in a growing number of published case reports, TJA patients present with cardiotoxicity and heart failure several years after surgery. Yet, the mechanisms and the magnitude of the risk are unknown. Large scale, population- based studies are needed to assess the potential contribution of chronic exposure to TJA implant debris and subtypes (cobalt/chromium, polyethylene) to the risk of cardiotoxicity and heart failure. We propose to leverage unique population-based data resources and the Mayo Clinic TJA registry to investigate cardiotoxicity in TJA patients. Using 5-decades of historical data from the REP, we will compare the risk of heart failure in population-based cohorts of TJA patients and matched non-TJA subjects adjusting for well- known confounders. We will further examine the risk according to implant types. We will retrieve historical echocardiographic data to compare cardiac structure and function measures in TJA patients and controls. Finally, we will correlate metal ion levels with cross-sectional and longitudinal cardiac structure and function measures in TJA patients. Successful completion of the proposed series of studies will be a key step towards understanding whether chronic exposure to TJA implants has adverse cardiac effects. Our unique data resources offer a rare opportunity to efficiently address this unknown risk. Potential downstream effects are significant including monitoring of high risk TJA implants and patients who are most likely to suffer from systemic cardiac effects.